Radiation therapy is a recommended course of treatment for many individuals who are diagnosed with breast cancer. Typically, the breast is irradiated after breast-conserving lumpectomies, while the chest wall is irradiated following mastectomy, with or without regional lymph node irradiation. Adjuvant radiation is considered to confer a potential survival advantage and an improvement in local cancer control. Women with node positive breast cancer benefit from comprehensive nodal irradiation, which encompasses larger volumes of normal tissues, including the heart. About four million women in the United States have been treated for breast cancer, the majority having received radiotherapy.
Interestingly, however, while survival data associated with radiation therapy initially indicated that adjuvant radiation conferred a cancer specific survival advantage, no advantage in overall survival was observed. Subsequent increased mortality due to coronary disease and other cardiac conditions has been noted in breast-cancer survivors who have undergone radiation therapy. It is now widely accepted that cardiac structures, including the coronary arteries, are radio-sensitive and vulnerable to damage from radiation that passes through the chest wall.
It has been difficult to quantify the effects of radiation on the heart for many reasons. Until about ten to fifteen years ago, computerized tomography (CT) scanning was not routinely used in radiation planning such that cardiac dose parameters were not available for data-mining and analysis. Further, it often takes many years for radiation-induced damage to cardiac tissue to manifest. By the time data is analyzed for cardiac risk associated with a particular treatment protocol, the treatment protocol may be outdated. According to one seminal study involving 4,456 women treated between 1954 and 1983, researchers found a 1.76-fold higher risk of cardiac disease and a 1.33-fold higher risk of dying from vascular disease among women treated for left-sided breast cancer as compared to those treated for right-sided breast cancer.
Despite advances in radiotherapeutic techniques and the widespread recommendation to radiation oncologists to take precautionary measures, the risk of radiation-related cardiac damage still exists, especially in cases of left-sided breast cancer. For example, in 2008 the radiation plans of 50 patients with left-sided breast cancer and five with right-sided breast cancer were evaluated and outcomes analyzed. Although the radiation dose to all cardiac structures was 1.2 to 2 Gray for right-sided patients, in half of those treated for left-sided cancer, at least part of the heart received a dose higher than 20 Gray. This higher dose has been shown to raise the risk of coronary artery stenosis in the mid- and distal left anterior descending artery, a common site of atherosclerosis leading to heart attack. According to the authors of the study, a 50-year-old woman with no cardiovascular risk factors has a 1.9 percent chance of dying of heart disease before she turns 80, and radiation treatment for breast cancer increases that risk to between 2.4 percent and 3.4 percent, depending on how much radiation exposure the heart receives.
Studies are underway to determine the tolerance doses for radiation that reaches the heart and coronary arteries; however, until formal guidelines are established, efforts to protect the heart and cardiac structures during radiation therapy remain critical to reducing the risk of long-term cardiac damage.
Further, many physicians specializing in women's health issues fear that women will construe the data to mean that it would be preferable to have their breasts removed instead of having lumpectomies, in order to avoid the cardio-damaging effects of radiation. Radiation therapy is generally recommended for women who elect to undergo breast-conserving treatments, such as lumpectomy; whereas, unless a patient is node-positive, radiation therapy is typically avoided when the patient elects a mastectomy. In fact, statistics suggest the fear of radiation damage is indeed influencing operative selection at least in the United States, where the rate of selection of mastectomy over lumpectomy is increasing, in cases where options for treatment exist.
Although most radiation oncologists attempt to avoid radiation exposure to the heart, the heart still receives some of the dose, especially when the left breast is treated. Radiation damage to the linings of blood vessels and scarring of the heart muscle continue to occur. According to a study out of Sweden and Denmark, the records of 2,168 women who had radiation therapy for breast cancer from 1958 to 2001 were analyzed. An alarming 963 of the women experienced major cardiac events sometime after their cancer treatment, defined as infarction or clogged coronary arteries that needed treatment or caused death. Based on inspection of the treatment records, it was determined that the risk began to increase within a few years after radiation exposure, and that the risk continued to increase for at least 20 years. The higher the radiation dose, the higher the risk, and there was some increase in risk at even the lowest level of radiation exposure. With each Gray to which the heart was exposed, the odds of heart attack or another coronary event rose by 7.4 percent. The average dose to the heart over an entire course of radiation therapy was 5 Gray. For an individual woman, the net effect would depend on her baseline initial risk of heart disease and the total radiation dose to the heart.
In accordance with more modern procedures, radiation oncologists report the dose to cardiac structures as less than 5 Gray and closer to 2 Gray. Many radiation oncologists routinely take precautionary measures, including placing external shields in front of the heart and attempting to curve radiation around the chest wall by irradiating from a side perspective rather than straight through the heart and lungs. Other recommended procedures for reducing exposure of secondary radio-sensitive tissues in the lumpectomy context include application of radiotherapy while the patient is in the prone position on a specially adapted table with openings permitting the breasts to fall away from the chest.
Breast brachytherapy is thought to avoid larger doses to secondary tissues and involves either 1) placing multiple catheters into the breast that surround the area where the excised tumor was located, or 2) placing a single catheter in the breast that contains a balloon that inflates once inside the breast, wherein a radioactive pellet is inserted into the catheter(s) on a dosing schedule for a number of days, after which the catheters are removed. Multicatheter brachytherapy is thought to afford the most targeted partial breast irradiation, but has several drawbacks, not the least of which is that radiation continues to reach cardiac tissue. Although the radiation is provided at a severely reduced level, exposure is across a sustained period of time. Further, this method is considered highly technical and is limited to patients with small, early tumors with well-defined borders.
Hence, there remains a need in the art for devices and methods effective for reducing the cardiovascular risk associated with radiotherapy of the chest region.